This study was designed to evaluate the biochemical basis for the life-threatening toxicity observed when 5-fluorouracil and sorivudine are coadministered. The study was designed to examine dihyropyrimidine dehydrogenase (DPD) activity in peripheral blood mononuclear (PBM) cells collected from patients at specified times after administration of a typical daily dose of sorivudine (such as is used to treat herpes zoster). The study demonstrated in three patients that DPD activity was rapidly and markedly decreased (to essentially "O") after administration of sorivudine. Such a decrease would be expected to produce decreased clearance of 5-fluorouracil, if it were concurrently administered, and lead to increased 5-fluorouracil toxicity.